Sunday, October 4, 2015

The Problem With Benzodiazepines.....

I want to thank David Allen for the inspiration for this post when he commented that as an addiction psychiatrist, I was probably seeing a skewed sample of people addicted to benzodiazepines and that might be why I have such a jaundiced view of them. I use the above bubble diagram to illustrate how benzodiazepines are prescribed by docs like me with a strong bias toward preventing addiction compared with physicians who have no such bias. To make sure that we are on the same page, benzodiazepines are all technically tranquilizers or sedatives. They marked a therapeutic advance from the earlier barbiturate class in that their therapeutic index (ratio of the drug that produces toxicity in 50% of patients to the dose that produces a therapeutic response in 50% of patients) is much greater than earlier tranquilizers like barbiturates. The practical measure is that it takes much higher doses to produce respiratory arrest and death. Despite the increased safety these drugs are addictive. People can develop a tolerance and in some people they produce a euphorigenic effect, very similar to the effect of alcohol. Some people describe benzodiazepines as "alcohol in a pill." Unfortunately we do not know the percentage of people where that occurs or how to detect them. There are many common clinical situations where the safety margin of benzodiazepines is cancelled out by other factors. Mixing them with alcohol and opiates are two of the most common dangerous situations and if you are treating addiction - you see that happen all of the time.

Rather than list the entire table of benzodiazepines, I am going to list the commonest ones that I see being abused. In order from the most frequently abuse that group would include alprazolam (Xanax), lorazepam (Ativan), clonazepam (Klonopin), and diazepam (Valium). Of those compounds Xanax Bars or 2 mg alprazolam tablets seem to be the most commonly abused by far. The maximum recommended dose of alprazolam is 4 mg/day and I frequently have seen people taking 8-20 mg/day in combination with other street drugs. Benzodiazepines have all been generic for a long time so they are very inexpensive to purchase if you have a prescription. If you don't have a prescription and acquire them illegally the "street value" of a drug is a sign of abusability. The average street value of alprazolam is about $5 for a 2 mg bar. The immediate risk of using benzodiazepines excessively is accidentally overdosing on the single drug or in combination with alcohol and other drugs of abuse. There is also a significant seizure risk from abrupt withdrawal when the supply of medications have been used. The abuse of benzodiazepine like compounds that are more typically used for sleep like zolpidem (Ambien) or eszopiclone (Lunesta) does happen but it is more likely to occur in combination with alcohol for alcohol related insomnia. A common example would be a person with alcohol dependence who takes zolpidem at night so that they can sleep through the entire night. Without it they would predictably wake up at 2 or 3 AM from the withdrawal effects of alcohol. Chronic use of benzodiazepines whether by prescription or acquisition from illegal sources can lead to tolerance and chronic withdrawal symptoms that can last for months if the drug or medication is stopped. That fact alone should be considered as part of the risk of taking benzodiazepines - even in the situation where the person does not have an addiction and has anxiety that they do not believe can be treated by any other means. In my experience, I am not sure that kind of anxiety exists.

Another common problem with benzodiazepines is that they can be psychologically debilitating, even if the person affected never takes the pill. It is all part of the behavioral pharmacology of addicting drugs. It usually starts out with a panic attack. That panic attack can result in people going to the emergency department once or twice because they believe they are having a heart attack. Somewhere along the line a physician prescribes alprazolam to take "in case of a panic attack." That starts to happen and even if the panic attacks are rare, brief, and situational - the person affected starts to believe they need to carry alprazolam around with them wherever they go "in case" of another panic attack. They may not have had a panic attack in years, but they are more anxious about whether they are carrying a pill when they get on a plane, cross a bridge, etc. The pill have taken on Talisman-like features based on their using it for a condition that for most people fades away over time. Some who don't know the sequence of events might suggest "what's the harm" if somebody develops such a belief system around a pill. In my estimation the harm is that the person's normal conscious state has been transformed and they have exchanged one form of anxiety for another. The debilitating effects of anxiety depend on the illusion that your life needs to be modified in a certain way to accommodate it. Proving to yourself that is not true is one of the best ways to adapt.

Despite those reservations, I have prescribed a lot of benzodiazepines in my career. They are very good medications to use in controlled environments for acute alcohol and sedative hypnotic withdrawal, acute seizures, catatonia, akathisia, and various agitation syndromes associated with acute psychosis and mania. The goal is typically to get the patient off the medication before they are discharged and to avoid treating patients with addiction with benzodiazepines. Benzodiazepines are also useful for the first month in treating panic attacks, but that typically takes a lot of work. The work involved is convincing the patient that a medication that seems to work rapidly is not a good one to take for the long haul. The other dimension that is operating here that is rarely commented on and never explicit is whether the person receiving the benzodiazepine enjoys taking it. Medications that are potentially addictive lead to an array of problems that are not there with drugs than are not addicting. The main one is that they tend to be viewed as solutions for everything. Instead of just anxiety or panic people will take them for insomnia, stress, or just to wind down at the end of the day. Medications that reinforce their own use have the problem of inventing new uses that they were never prescribed for and that can lead to escalating doses of the medication. In some complicated situations benzodiazepines are added to treat anxiety. They have been used in psychiatric patients with multiple problems and been shown to add no benefit. They are commonly added to multiple medications including opioids in patients with chronic pain with no additional benefit.

Benzodiazepines are a big problem in primary care. The NSDUH survey illustrates that most people with an addiction are not aware of it and further that only a small minority seek treatment and find it. That same survey suggests that about 1.5 million Americans start using tranquilizers and sedatives (they do not have a unique benzodiazepine category) for non-medical use very year. Even if it is apparent to a primary care physician and their patient that an addiction to benzodiazepines exits, there are significant obstacles to reversing the process. Although there are protocols for slowly tapering the medication on the Internet, it takes a very highly motivated person and ideal circumstances to accomplish this. Outpatient detox from urgent care, the emergency department or an outpatient clinic is problematic because the same medication that the patient is not able to control is being given to them to self administer at home. It is common that the detox medications are all taken the same day or in some cases at once. Structured detoxification in the American health care system is practically impossible to find, especially in the case of benzodiazepines that require careful attention to seizure prevention, the prevent of withdrawal delirium, and adequate treatment of chronic withdrawal symptoms when they emerge. Some primary care clinics are taking the preventive approach of not starting benzodiazepines in the first place.

There is a lot of resistance to the ideas of addiction docs when benzodiazepines and their long term effects are discussed among physicians. There is always a physician who claims that they have successfully treated a person with an alcohol use disorder with benzodiazepines or they have people who have stayed on low doses for decades in order to treat their anxiety. I see the failures. It leads to the question of how many people are capable of staying sober, not developing a tolerance to benzodiazepines, and not experiencing a negative impact on their life.

As far as I know there are no good studies that address that question and I would not expect that there will be. Any study that allowed subjects to mix alcohol, opiates, and benzodiazepines would be unethical and should not be approved by any Human Subjects Committee.

George Dawson, MD, DFAPA

Supplementary:

This article was subsequently edited and modified for the Psychiatric Times. The edited version reads better.